Evaluation of Antibody Responses in Patients with B-Cell Malignancies after Two and Three Doses of Anti-SARS-CoV-2 S Vaccination—A Retrospective Cohort Study

SIMPLE SUMMARY: Patients with B-cell malignancies benefit from the third vaccination against SARS-CoV-2 with regards to antibody production. In this cohort, patients with B-cell malignancies experienced greater difficulties in developing neutralizing antibodies, particularly under active treatment with anti-CD19 CAR T-cells or anti-CD20 monoclonal antibodies. Nevertheless, the third dose achieved an enhancement of the serological responses and increased humoral immunity. These observations are in line with recent studies. Future studies with larger cohorts on this research topic will broaden the understanding of an effective anti-SARS-CoV-2 vaccination scheme and guide the timing for upcoming booster vaccinations in high-risk hematological patients. Additionally, future studies should also include data on circulating B- and T-cells in order to gain a more complete picture of the immune system of patients with B-cell malignancies upon different treatments and their influence on immune protection in response to vaccinations. ABSTRACT: Patients with B-cell malignancies are at a higher risk of severe SARS-CoV-2 infections. Nevertheless, extensive data on the immune responses of hematological patients and the efficacy of the third dose of the vaccine are scarce. The goal of this study was to determine standardized anti-SARS-CoV-2 S antibody levels and to evaluate differences between treatment modalities in response to the second and third vaccines among patients with B-cell malignancies treated at the University Hospital Krems and the University Hospital of Vienna. The antibody levels of a total of 80 patients were retrospectively analyzed. The results indicate a significant increase in antibody production in response to the third vaccination. The highest increases could be observed in patients in a “watchful-waiting” and “off-therapy” setting. Encouragingly, approximately one-third of patients who did not develop antibodies in response to two vaccinations achieved seroconversion after the third vaccination. “Watchful-waiting”, “off-therapy” and treatment with BTK inhibitors were indicative for increased antibody response after the third dose compared to anti-CD19 CAR T-cell and anti-CD-20 antibody treatment. In summary, the results of this study underline the pre-eminent role of the need for complete vaccination with three doses for the development of protective immunity in patients with B-cell malignancies.